tbuckley/cabot-search huggingface dataset:
Cephalic inferior vena cava non-clamping technique versus standard procedure for robot-assisted laparoscopic level II–III thrombectomy: a prospective cohort study
Authors: Yu Zhang, Hai Bi, YunJie Fu, HongXian Zhang, ShuDong Zhang, Ke Liu, Lei Liu, Nan Li, Cheng Liu, XiaoJun Tian, LuLin Ma
Journal: International Journal of Surgery (2023)

Background: Renal tumour can invade the venous system and ~4–10% patients with renal tumour had venous thrombus. Although the feasibility of robot-assisted laparoscopic inferior vena cava thrombectomy (RAL-IVCT) in patients with inferior vena cava (IVC) thrombus has been validated, the wide application is still a challenge due to the complexity of IVC control. The objective was to describe our novel cephalic IVC non-clamping technique and to compare the outcomes versus standard RAL-IVCT. Materials and methods: A prospective single-centre cohort containing 30 patients with level II–III IVC thrombus was established since August 2020. Fifteen patients underwent cephalic IVC non-clamping approach and 15 patients received standard RAL-IVCT. The authors decided the surgical technique according to the echocardiographic assessment of the right heart and IVC. Results: The non-clamping group had less operative time (median 148 versus 185 min, P =0.04), and lower Clavien-grade II complication rate (26.7% versus 80.0%, P =0.003). The median intraoperative blood loss were 400 ml [interquartile range (IQR) 275–615 mL] and 800 ml (IQR 350–1300 ml), respectively ( P =0.05). The most common complication in standard RAL-IVCT group was liver dysfunction. No gas embolism, hypercapnia or tumour thrombus dislodgment occurred in non-clamping group. After a median follow-up of 17.0 months (IQR 13.5–18.5 months) and 15.5 months (IQR 13.0–17.0 months), two patients (16.7%) in the non-clamping group and 3 patients (20.0%) in the standard RAL-IVCT group died (hazard ratio 0.59, 95% CI 0.10–3.54, P =0.55). Conclusions: The cephalic IVC non-clamping technique can be performed safely with acceptable surgical outcomes and short-term oncologic outcomes in patients with level II–III IVC thrombus. Compared with standard procedure, it had less operative time and lower complication rate.
Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1–Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial
Authors: Edward B. Garon, Alexander I. Spira, Sarah B. Goldberg, Jamie E. Chaft, Vassiliki Papadimitrakopoulou, Tina Cascone, Scott J. Antonia, Julie R. Brahmer, D. Ross Camidge, John D. Powderly, Antoinette J. Wozniak, Enriqueta Felip, Song Wu, Maria L. Ascierto, Nairouz Elgeioushi, Mark M. Awad
Journal: Journal of Thoracic Oncology (2023)

Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy. Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019. Durvalumab 20 mg/kg plus tremelimumab 1 mg/kg was administered intravenously every 4 weeks for four doses, followed by up to nine doses of durvalumab monotherapy every 4 weeks for up to 12 months of treatment or disease progression. Primary end points included safety and objective response rate (ORR) on the basis of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per blinded independent central review; secondary end points were ORR on the basis of RECIST v1.1 per investigator; duration of response, disease control, and progression-free survival on the basis of RECIST v1.1 per blinded independent central review and investigator; and overall survival. gov identifier: NCT02000947. PD-(L)1-refractory (n = 38) and PD-(L)1-relapsed (n = 40) patients were treated. The most common treatment-related adverse events were fatigue (26.3%, PD-(L)1-refractory patients) and diarrhea (27.5%, PD-(L)1-relapsed patients). Grade 3 to 4 treatment-related adverse events occurred in 22 patients. Median follow-up duration was 43.6 months for PD-(L)1-refractory patients and 41.2 months for PD-(L)1-relapsed patients. The ORR was 5.3% for PD-(L)1-refractory patients (one complete response, one partial response) and 0% for PD-(L)1-relapsed patients. Durvalumab plus tremelimumab had a manageable safety profile, but the combination did not have efficacy after PD-(L)1 treatment failure.
Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer
Authors: Chao Cheng, Thinh T. Nguyen, Mabel Tang, Xinan Wang, Chongming Jiang, Yanhong Liu, Ivan Gorlov, Olga Gorlova, John Iafrate, Michael Lanuti, David C. Christiani, Christopher I. Amos
Journal: Journal of Thoracic Oncology (2023)
Inhibition of C5AR1 impairs osteoclast mobilization and prevents bone loss
Authors: Carolina Pimenta-Lopes, Cristina Sánchez-de-Diego, Alexandre Deber, Andrea Egea-Cortés, José Antonio Valer, Albert Alcalá, Andrés Méndez-Lucas, Anna Esteve-Codina, Jose Luis Rosa, Francesc Ventura
Journal: Molecular Therapy (2023)

Age-related and chemotherapy-induced bone loss depends on cellular senescence and the cell secretory phenotype. However, the factors secreted in the senescent microenvironment that contribute to bone loss remain elusive. Here, we report a central role for the inflammatory alternative complement system in skeletal bone loss. Through transcriptomic analysis of bone samples, we identified complement factor D, a rate-limiting factor of the alternative pathway of complement, which is among the most responsive factors to chemotherapy or estrogen deficiency. We show that osteoblasts and osteocytes are major inducers of complement activation, while monocytes and osteoclasts are their primary targets. Genetic deletion of C5ar1, the receptor of the anaphylatoxin C5a, or treatment with a C5AR1 inhibitor reduced monocyte chemotaxis and osteoclast differentiation. Moreover, genetic deficiency or inhibition of C5AR1 partially prevented bone loss and osteoclastogenesis upon chemotherapy or ovariectomy. Altogether, these lines of evidence support the idea that inhibition of alternative complement pathways may have some therapeutic benefit in osteopenic disorders.
Socioeconomic Inequalities in Novel NSCLC Treatments During the Era of Tumor Biomarker-Guided Therapy: A Population-Based Cohort Study in a Publicly Funded Health Care System
Authors: Ruth P. Norris, Rosie Dew, Alastair Greystoke, Adam Todd, Linda Sharp
Journal: Journal of Thoracic Oncology (2023)

Socioeconomic inequalities in the utilization of conventional NSCLC treatments are well documented. Nevertheless, it is not known whether these inequalities are also observed with novel anticancer therapies. This study evaluated associations between deprivation and utilization of novel anticancer therapies targeting tumor biology, the immune system, or both, within the English national publicly funded health care system.
Predictors and barriers to vaccination among older Syrian refugees in Lebanon: a cross-sectional analysis of a multi-wave longitudinal study
Authors: Berthe Abi Zeid, Tanya El Khoury, Hala Ghattas, Marwan F Alawieh, Zeinab Ramadan, Sirine Anouti, Sawsan Abdulrahim, Stephen J McCall
Journal: The Lancet Healthy Longevity (2023)
Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank
Authors: Hongliang Feng, Lulu Yang, Sizhi Ai, Yue Liu, Weijie Zhang, Binbin Lei, Jie Chen, Yaping Liu, Joey W Y Chan, Ngan Yin Chan, Xiao Tan, Ningjian Wang, Christian Benedict, Fujun Jia, Yun Kwok Wing, Jihui Zhang
Journal: The Lancet Healthy Longevity (2023)

BackgroundThe health effects of rest–activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest–activity rhythm amplitude and health risks among the general UK population.MethodsWe did a prospective cohort analysis of UK Biobank participants aged 43–79 years with valid wrist-worn accelerometer data. Low rest–activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest–activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest–activity rhythm amplitude and outcomes using Cox proportional hazards models.FindingsBetween June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56–69) were recruited. Median follow-up was 6·4 years (IQR 5·8–6·9). Decreased rest–activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05–1·16]), cancer (1·08 [1·01–1·16]), infectious diseases (1·31 [1·22–1·41]), respiratory diseases (1·26 [1·19–1·34]), and digestive diseases (1·08 [1·03–1·14]), as well as all-cause mortality (1·54 [1·40–1·70]) and disease-specific mortality (1·73 [1·34–2·22] for cardiovascular diseases, 1·32 [1·13–1·55] for cancer, and 1·62 [1·25–2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest–activity parameters, low rest–activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes.InterpretationOur results suggest that low rest–activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest–activity rhythm to improve health and longevity.FundingNational Natural Science Foundation of China and China Postdoctoral Science Foundation.
The inverse care law and COVID-19 vaccination for refugees
Authors: Elias Kondilis, Valentina Gallo
Journal: The Lancet Healthy Longevity (2023)

A perquisite for achieving high COVID-19 vaccine uptake, not only among refugees and migrants but also in populations as a whole, is the ability of public health authorities to monitor and understand the emerging barriers and facilitators determining vaccine rollout.1 The study in The Lancet Healthy Longevity by Berthe Abi Zeid and colleagues2 is a welcome contribution to this demanding and challenging field of policy practice. Their research reports low COVID-19 vaccine uptake rates among Syrian refugees aged 50 years or older residing in Lebanon (1235 [42·5%] of 2906 participants interviewed up to March 14, 2022), and low vaccine acceptance rates among this vulnerable population group (38·1% of unvaccinated refugees were unwilling to receive the vaccine and 40·1% remained hesitant due to a fear of side-effects).
Association of early life physical and sexual abuse with premature mortality among female nurses: prospective cohort study
Authors: Yi-Xin Wang, Yang Sun, Stacey A Missmer, Kathryn M Rexrode, Andrea L Roberts, Jorge E Chavarro, Janet W Rich-Edwards
Journal: BMJ (2023)

To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years).Prospective cohort study.The Nurses' Health Study II (2001-19).67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001.Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models.2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality.Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality.
Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study
Authors: Anthony Ravussin, Anna Hayman Robertson, Asia-Sophia Wolf, Kristine Blix, Ingrid Fadum Kjønstad, Guri Solum, Berit Feiring, Bjørn Heine Strand, Fridtjof Lund-Johansen, Ludvig A Munthe, Per Magnus, Lill Trogstad, Siri Mjaaland
Journal: The Lancet Healthy Longevity (2023)

BackgroundOlder age is associated with poorer outcomes to COVID-19 infection. The Norwegian Institute of Public Health established a longitudinal cohort of adults aged 65–80 years to study the effects of the COVID-19 pandemic. Here we describe the characteristics of the cohort in general, and specifically the immune responses at baseline and after primary and booster vaccination in a subset of longitudinal blood samples, and the epidemiological factors affecting these responses.Methods4551 participants were recruited, with humoral (n=299) and cellular (n=90) responses measured before vaccination and after two and three vaccine doses. Information on general health, infections, and vaccinations were obtained from questionnaires and national health registries.FindingsHalf of the participants had a chronic condition. 849 (18·7%) of 4551 were prefrail and 184 (4%) of 4551 were frail. 483 (10·6%) of 4551 had general activity limitations (scored with the Global Activity Limitation Index). After dose two, 295 (98·7%) of 299 participants were seropositive for anti-receptor binding domain IgG, and 210 (100%) of 210 participants after dose three. Spike-specific CD4 and CD8 T cell responses showed high heterogeneity after vaccination and responded to the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529 or BA.1) variants of concern. Cellular responses to seasonal coronaviruses increased after SARS-CoV-2 vaccination. Heterologous prime boosting with mRNA vaccines was associated with the highest antibody (p=0·019) and CD4 T cell responses (p=0·003), and hypertension with lower antibody levels after three doses (p=0·04).InterpretationMost older adults, including those with comorbidities, generated good serological and cellular responses after two vaccine doses. Responses further improved after three doses, particularly after heterologous boosting. Vaccination also generated cross-reactive T cells against variants of concern and seasonal coronaviruses. Frailty was not associated with impaired immune responses, but hypertension might indicate reduced responsiveness to vaccines even after three doses. Individual differences identified through longitudinal sampling enables better prediction of the variability of vaccine responses, which can help guide future policy on the need for subsequent doses and their timing.FundingNorwegian Institute of Public Health, Norwegian Ministry of Health, Research Council of Norway, and Coalition for Epidemic Preparedness Innovations.
How should we evaluate the efficacy of endoscopic closure appropriately? A black box between interventions and outcomes
Authors: Osamu Goto
Journal: Endoscopy (2023)

Endoscopic closure has drawn attention owing to the development and clinical introduction of various endoscopic interventions in the gastrointestinal tract. A mucosal closure is expected to prevent postoperative adverse events, such as bleeding and delayed perforation, in endoscopic intraluminal resection, for example endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Endoscopic full-thickness resection always necessitates a robust and sustained defect closure. Furthermore, gastrointestinal fistula requires a closure method that is less invasive than surgical interventions. Intentionally created defects become wider, deeper, and harder to close with only conventional methods using endoscopic clips owing to therapeutic endoscopic expansion. Therefore, dedicated suturing devices/techniques need to be further developed.
Inhibition of Importin-α–Mediated Nuclear Localization of Dendrin Attenuates Podocyte Loss and Glomerulosclerosis
Authors: Maulana A. Empitu, Mitsuhiro Kikyo, Naritoshi Shirata, Hiroyuki Yamada, Shin-ichi Makino, Ika N. Kadariswantiningsih, Masashi Aizawa, Jaakko Patrakka, Katsuhiko Nishimori, Katsuhiko Asanuma
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Nuclear translocation of dendrin is observed in injured podocytes, but the mechanism and its consequence are unknown. In nephropathy mouse models, dendrin ablation attenuates proteinuria, podocyte loss, and glomerulosclerosis. The nuclear translocation of dendrin promotes c-Jun N -terminal kinase phosphorylation in podocytes, altering focal adhesion and enhancing cell detachment–induced apoptosis. We identified mediation of dendrin nuclear translocation by nuclear localization signal 1 (NLS1) sequence and adaptor protein importin- α . Inhibition of importin- α prevents nuclear translocation of dendrin, decreases podocyte loss, and attenuates glomerulosclerosis in nephropathy models. Thus, inhibiting importin- α –mediated nuclear translocation of dendrin is a potential strategy to halt podocyte loss and glomerulosclerosis. Background Nuclear translocation of dendrin is observed in the glomeruli in numerous human renal diseases, but the mechanism remains unknown. This study investigated that mechanism and its consequence in podocytes. Methods The effect of dendrin deficiency was studied in adriamycin (ADR) nephropathy model and membrane-associated guanylate kinase inverted 2 ( MAGI2 ) podocyte-specific knockout ( MAGI2 podKO) mice. The mechanism and the effect of nuclear translocation of dendrin were studied in podocytes overexpressing full-length dendrin and nuclear localization signal 1–deleted dendrin. Ivermectin was used to inhibit importin- α . Results Dendrin ablation reduced albuminuria, podocyte loss, and glomerulosclerosis in ADR-induced nephropathy and MAGI2 podKO mice. Dendrin deficiency also prolonged the lifespan of MAGI2 podKO mice. Nuclear dendrin promoted c-Jun N -terminal kinase phosphorylation that subsequently altered focal adhesion, reducing cell attachment and enhancing apoptosis in cultured podocytes. Classical bipartite nuclear localization signal sequence and importin- α mediate nuclear translocation of dendrin. The inhibition of importin- α / β reduced dendrin nuclear translocation and apoptosis in vitro as well as albuminuria, podocyte loss, and glomerulosclerosis in ADR-induced nephropathy and MAGI2 podKO mice. Importin- α 3 colocalized with nuclear dendrin in the glomeruli of FSGS and IgA nephropathy patients. Conclusions Nuclear translocation of dendrin promotes cell detachment–induced apoptosis in podocytes. Therefore, inhibiting importin- α –mediated dendrin nuclear translocation is a potential strategy to prevent podocyte loss and glomerulosclerosis.
Re: Gabriela Ilie, Ricardo Rendon, Ross Mason, et al. A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.02.009
Authors: Mauricio Plata, Diaz Ritter Cesar, Nicolás Badillo
Journal: European Urology (2023)
Role of Oxygen Starvation in Right Ventricular Decompensation and Failure in Pulmonary Arterial Hypertension
Authors: Marta Oknińska, Karolina Zajda, Zuzanna Zambrowska, Małgorzata Grzanka, Aleksandra Paterek, Urszula Mackiewicz, Cezary Szczylik, Marcin Kurzyna, Agnieszka Piekiełko-Witkowska, Adam Torbicki, Claudine Kieda, Michał Mączewski
Journal: JACC Heart Failure (2023)
A Randomized Crossover Trial to Compare Automated Insulin Delivery (the Artificial Pancreas) With Carbohydrate Counting or Simplified Qualitative Meal-Size Estimation in Type 1 Diabetes
Authors: Ahmad Haidar, Laurent Legault, Marie Raffray, Nikita Gouchie-Provencher, Adnan Jafar, Marie Devaux, Milad Ghanbari, Rémi Rabasa-Lhoret
Journal: Diabetes Care (2023)

OBJECTIVE Qualitative meal-size estimation has been proposed instead of quantitative carbohydrate (CHO) counting with automated insulin delivery. We aimed to assess the noninferiority of qualitative meal-size estimation strategy. RESEARCH DESIGN AND METHODS We conducted a two-center, randomized, crossover, noninferiority trial to compare 3 weeks of automated insulin delivery with 1) CHO counting and 2) qualitative meal-size estimation in adults with type 1 diabetes. Qualitative meal-size estimation categories were low, medium, high, or very high CHO and were defined as &amp;lt;30 g, 30–60 g, 60–90 g, and &amp;gt;90 g CHO, respectively. Prandial insulin boluses were calculated as the individualized insulin to CHO ratios multiplied by 15, 35, 65, and 95, respectively. Closed-loop algorithms were otherwise identical in the two arms. The primary outcome was time in range 3.9–10.0 mmol/L, with a predefined noninferiority margin of 4%. RESULTS A total of 30 participants completed the study (n = 20 women; age 44 (SD 17) years; A1C 7.4% [0.7%]). The mean time in the 3.9–10.0 mmol/L range was 74.1% (10.0%) with CHO counting and 70.5% (11.2%) with qualitative meal-size estimation; mean difference was −3.6% (8.3%; noninferiority P = 0.78). Frequencies of times at &amp;lt;3.9 mmol/L and &amp;lt;3.0 mmol/L were low (&amp;lt;1.6% and &amp;lt;0.2%) in both arms. Automated basal insulin delivery was higher in the qualitative meal-size estimation arm (34.6 vs. 32.6 units/day; P = 0.003). CONCLUSIONS Though the qualitative meal-size estimation method achieved a high time in range and low time in hypoglycemia, noninferiority was not confirmed.
Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial
Authors: Athena Philis-Tsimikas, Marisse Asong, Edward Franek, Ting Jia, Julio Rosenstock, Karolina Stachlewska, Hirotaka Watada, Monika Kellerer
Journal: The Lancet Diabetes & Endocrinology (2023)